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  • Brief Communications Arising
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Another explanation for apparent epistasis

Nature volume 514, pages E3–E5 (2014)Cite this article

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Abstract

Arising from G. Hemani et al. Nature 508, 249–253 (2014); doi:10.1038/nature1300510.1038/nature13005

Epistasis occurs when the effect of a genetic variant on a trait is dependent on genotypes of other variants elsewhere in the genome. Hemani et al. recently reported the detection and replication of many instances of epistasis between pairs of variants influencing gene expression levels in humans1. Using whole-genome sequencing data from 450 individuals we strongly replicated many of the reported interactions but, in each case, a single third variant captured by our sequencing data could explain all of the apparent epistasis. Our results provide an alternative explanation for the apparent epistasis observed for gene expression in humans. There is a Reply to this Brief Communication Arising by Hemani, G. et al. Nature 514, http://dx.doi.org/10.1038/nature13692 (2014).

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Figure 1: Haplotype and linkage disequilibrium structure.

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Authors and Affiliations

  1. Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter EX2 5DW, UK,

    Andrew R. Wood, Marcus A. Tuke, David Melzer, Timothy M. Frayling & Michael N. Weedon

  2. Laboratory of Neurogenetics, National Institute of Aging, Bethesda, 20892, Maryland, USA

    Mike A. Nalls, Dena G. Hernandez & Andrew B. Singleton

  3. Department of Molecular Neuroscience and Reta Lila Laboratories, Institute of Neurology, UCL, London WC1N IPJ, UK,

    Dena G. Hernandez

  4. I.O.T. and Department of Medical and Surgical Critical Care, Tuscany Regional Health Agency, Florence, Italy, University of Florence, Florence, Italy

    Stefania Bandinelli

  5. Geriatric Unit, Azienda Sanitaria di Firenze, Florence, Italy

    Stefania Bandinelli

  6. Longitudinal Studies Section, Clinical Research Branch, Gerontology Research Center, National Institute on Aging, Baltimore, 21225, Maryland, USA

    Luigi Ferrucci

Authors
  1. Andrew R. Wood
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  2. Marcus A. Tuke
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  3. Mike A. Nalls
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  4. Dena G. Hernandez
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  5. Stefania Bandinelli
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  6. Andrew B. Singleton
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  7. David Melzer
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  8. Luigi Ferrucci
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  9. Timothy M. Frayling
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  10. Michael N. Weedon
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Contributions

A.R.W., T.M.F. and M.N.W. designed the study. A.R.W., M.A.T. and M.N.W. performed the bioinformatics analyses. M.A.N., D.G.H., S.B., A.B.S., D.M. and L.F. provided the Inchianti study and expression data. A.R.W., T.M.F. and M.N.W. wrote the manuscript. All authors commented on the manuscript.

Corresponding authors

Correspondence to Timothy M. Frayling or Michael N. Weedon.

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Wood, A., Tuke, M., Nalls, M. et al. Another explanation for apparent epistasis. Nature 514, E3–E5 (2014). https://doi.org/10.1038/nature13691

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